We seek to a establish a research network that will facilitate clinical research in rare lung diseases by 1) promoting collaboration among centers already focused to clinical research on rare lung diseases, 2) attracting & training highly qualified investigators, 3) collecting clinical data from geographically distributed patients into a large, centralized database, and 4) making the accumulated clinical data available to those affected or possibly affected by a rare lung disease, their clinicians, clinical and basic investigators and the general public. Disorders chosen for the initial focus of this network include: alpha-1 antitrypsin deficiency (AATD), lymphangioleiomyomatosis (LAM), pulmonary alveolar proteinosis (PAP) and hereditary idiopathic pulmonary fibrosis (hIPF). The network consists of clinical centers in Ohio (the coordinating center), Colorado, Florida, Maryland, Massachusetts, Oregon, South Carolina and Texas, as well as in Japan and Australia. Centers are required to have and maintain an exemplary record of active clinical research and an adequate rare lung disease patient base. Participating patient support groups include the Alpha-1 Foundation, LAM Foundation and the Pulmonary Fibrosis Foundation. Many of these centers already work together closely. These centers and Foundations are also already closely integrated. For example, the Scientific Directors of all three participating foundations are active clinical investigators at clinical sites within the network. Furthermore, clinical sites were chosen from three currently active networks of collaborating clinical centers that include over 50 sites in 24 states distributed throughout the United States. All participating domestic clinical sites are associated with an active, NIH-supported general clinical research center (GCRC). Each center provides components required of the proposed network including ongoing longitudinal clinical studies, an excellent clinical training program, an active clinical research trials program designed to test novel therapies, develop diagnostic tests or evaluate outcome measures for rare lung diseases. Each of the Foundations provide education for patients, the lay public and the medical community. Importantly, one consequence of preparing this application has been the formation of the "Rare Lung Disease Foundation Consortium," which permits patient support groups with greater infrastructure to "nurture" the growth of less well-developed groups. It also provides support for individuals affected by a rare lung disease for which there is currently no foundation. Ongoing clinical, basic and translational studies at the centers chosen have already yielded critical insights into molecular mechanisms underlying lung function and defense in health and disease.